Glioma-Associated Oncogene 2 (GLI2) is a member of the GLI zinc finger-containing transcription factors, which are involved in cell-fate determination, proliferation and patterning in many cell types and most organs. The human GLI2 mRNA is known to undergo alternative splicing to create alternative splice variants. Transgenic mice over-expressing GLI2 in cutaneous keratinocytes develop multiple basal cell carcinomas, indicating a GLI2 role in the development of these carcinomas.
U.S. Pat. No. 6,440,739 and WO03/008545 disclose a range of 2′-methoxyethyl-modified chimerical antisense oligonucleotides targeting GLI2, and indicate that these may be useful in the treatment of diseases associated with GLI2 expression. Kim et al., 2007, Cancer Res. 67(8) 3583-3593 reports on 2′-methoxyethyl-modified chimerical antisense oligonucleotides which were used to specifically down-regulate GLI2 and decrease proliferation of hepatocellular carcinoma cells in vitro.
There is a need for improved oligomers targeting GLI2. There is also a need for oligomers targeting both GLI1 and GLI2.
Furthermore, there is a continuing need for new and improved approaches for treating and preventing acute myeloid leukemia and preleukemic disorders which is addressed by the present invention.